The term biorhythm, introduced in the early 20th century by Wilhelm Fliess, a German otolaryngologist and associate of Sigmund Freud, refers to the supposed existence of universal and deterministic biological cycles governing human physical, emotional, and intellectual capacities. Fliess proposed that human behavior and physical performance follow fixed 23-day (physical), 28-day (emotional), and 33-day (intellectual) cycles - sinusoidal and predetermined from birth. Despite the lack of experimental validation and the absence of any identified physiological mechanisms, this term continues to appear in contemporary scientific literature, where it is often used imprecisely to designate validated biological rhythms such as circadian variations. This article constitutes a narrative critical review with historical and epistemological analysis rather than a systematic review conducted under PRISMA guidelines. It analyzes the historical origin of the concept of biorhythm, the reasons for its lexical persistence, and the epistemological risks it poses to scientific rigor. The review aims to clarify the distinction between the pseudoscientific concept of biorhythms and scientifically validated biological rhythms studied in modern chronobiology. By comparing this concept with the biological rhythms recognized by modern chronobiology - circadian, ultradian, and infradian - which have measurable physiological correlates, and by examining its use in interpreting the biological effects of environmental factors, we highlight how scientifically inappropriate the term biorhythm is. Modern chronobiology provides a mechanistic, measurable, and falsifiable framework for studying physiological rhythms and their environmental modulation. Beyond its historical inadequacy, the continued use of the term also generates terminological redundancy and conceptual ambiguity, since validated chronobiological terminology already offers precise and operational descriptors of biological periodicity. The abandonment of the term "biorhythm" in the scientific literature appears necessary to preserve conceptual clarity and methodological validity, particularly in a cross-disciplinary field such as chronobiology.
Wearable light loggers and optical radiation dosimeters are increasingly used in chronobiology and circadian health research, yet their data often lack contextual information (e.g., sleep, activity, environmental conditions) and may be compromised by non-wear periods, compliance issues, or technical faults. To address these limitations, we conducted interviews (n = 21) and a survey (n = 16) with domain experts to distil and iteratively develop auxiliary data and quality-control strategies aimed at improving the accuracy and interpretability of wearable light measurements. From this process, we established a six-domain auxiliary data framework encompassing wear/non-wear logging, sleep monitoring, light-source context, participant behaviour, user experience, and environmental light levels. Survey responses showed strong consensus on the value of auxiliary information (importance 4.0/5), with sleep and wear-time tracking rated as the most essential additions. To support practical adoption, we provide implementation tools, including extensions to the open-source R package LightLogR, enabling streamlined integration of wearable and auxiliary data as well as systematic quality assurance and control. Experts agreed that combining contextual records with rigorous QA/QC procedures substantially improves the reliability of field-collected light-exposure data. These recommendations and tools aim to help researchers in chronobiology, wearable sensing, and health sciences maximise data quality and enhance interpretation in real-world light-exposure studies.
The nighttime ambient environment in which humanity sleeps is heating up due to human-induced climatic changes. Convergent global observational evidence links higher ambient temperatures to accelerated sleep impacts within-individuals, while in-lab evidence confirms that high temperatures mechanistically harm sleep initiation and maintenance. Despite marked methodological and evidentiary advances, the global sensitivity of sleep health to climate impact drivers remains imprecisely characterized and conservatively estimated. Indeed, we show that prior observational temperature and sleep research is nonrepresentative of the global human population, and that the most vulnerable remain undersampled despite evidence of their likely greater sleep sensitivity to heat. Here we sound a worldwide wake-up call for the sleep, climate and health research communities to address these needs through the formation of a global climate and sleep taskforce. This effort can perform a unified global assessment of climate-sleep relationships, impact pathways, and adaptation options in a variable and warming world. It can seek to integrate sleep health and methodological advances into global climate and health monitoring systems and economic assessments, and to translate these findings into scalable action. Persistent climate-sleep impacts and their downstream consequences to human health, wellbeing and performance warrant urgent study, mitigation and adaptation at the same global scale and across all levels of society. The international sleep research community must now act with the rigor, attention and resources needed to protect our nights.
Anomalies of the circadian rhythm are important in mental illnesses such as anxiety, schizophrenia, bipolar disorder, and depression. Dysregulated molecular clock genes, including CLOCK, BMAL1, PER, and CRY, are frequently linked to disturbances in hormone production, sleep-wake cycles, and neurotransmitter modulation. These genes affect mood, thought, and behaviour by controlling the body's internal clock. Circadian system dysfunctions can worsen mental health issues by impairing cognitive function, mood swings, and sleep patterns. Restoring circadian stability is the goal of chronobiology-based therapies. Bipolar illness and seasonal affective disorder (SAD) are two mood disorders that are commonly treated using light therapy. Supplementing with melatonin aids in the regulation of sleep patterns, and chronotherapy methods like wake therapy and sleep phase shifting can quickly alleviate depression symptoms. Pharmacological drugs that target circadian rhythms may improve therapeutic efficacy, according to recent studies. Managing mental illnesses may be possible by coordinating behavioural and medicinal treatments with circadian cycles. Psychiatric care must address circadian disturbance since it can improve mood stability, cognitive function, and general health. There is potential to improve the outcomes of psychiatric disorders by comprehending molecular clock mechanisms and incorporating chronotherapeutic techniques.
The COVID-19 pandemic profoundly disrupted daily life, including sleep behaviour. While several international studies report longer sleep durations during lockdown, most relied on convenience samples and only few influencing factors were considered. The aim of this study was to identify correlates of weekday sleep duration before and during Austria's first lockdown using two population-based cross-sectional surveys. Data were drawn from online surveys in September 2017 (n = 784) and May 2020 (n = 847), weighted to match the Austrian adult population by age and sex. Weekday sleep duration was derived from self-reported bed and wake times. Weighted linear regression models were fitted using backward elimination to select among known and suspected correlates of sleep duration. In 2020, additional COVID-specific covariables were considered. Covariable selection stability was assessed via bootstrapping. Compared to 2017, sleep duration increased in 2020 by 40 min (95% CI 27-55). Several covariables (minimum required sleep, work schedule, dinner time, chronotype, and diagnosed sleep disorder, education level and smoking status) were consistently retained in the selection models in both survey years. In 2020, COVID-specific factors such as changes in sleep quality, emotional burden during lockdown, and attitude toward the future further explained variation in sleep duration. Inclusion of these variables increased the adjusted model fit (R2) from 0.26 to 0.31. Beyond established determinants, COVID-related factors contributed substantially to explain variation in sleep duration during the lockdown. Our findings underscore the importance of incorporating context-specific covariables in future surveys to capture behavioural adaptations, e.g. during societal crises.
The increasing consumption of high-fat, energy-dense diets has contributed to the global rise in obesity and related chronic diseases. Fat preference is a multifactorial behavior potentially influenced by circadian rhythms and sleep-related factors. We aimed to investigate how these factors are associated with spontaneous preferences for high-fat foods among university students (n = 395). Fat preference was assessed using the Fat Preference Questionnaire (FPQ), sleep quality with the Pittsburgh Sleep Quality Index, chronotype with the Morningness - Eveningness Questionnaire, and physical activity with the International Physical Activity Questionnaire. Participants (73.6% female; mean age 21.17 ± 1.74 y; mean Body Mass Index (BMI) 21.76 ± 3.66 kg/m2) showed significant gender differences: males had higher TASTE and FREQ scores (p < 0.001), whereas females had higher DIFF scores (p = 0.004). DIFF scores differed between normal-weight individuals and those with overweight (p = 0.016). BMI was positively correlated with TASTE score overall and in males, and with DIFF score in females (p < 0.05). Chronotype had a weak but significantly negative correlation with TASTE and FREQ scores (p < 0.05) and was inversely associated with sleep quality (p < 0.001). Physical activity was not significantly associated with fat preference indices. Fat preference appears to be influenced by gender, BMI, chronotype, and nutrition-related education. Circadian-informed and behaviorally tailored interventions may support strategies to reduce high-fat food consumption.
Night work disrupts the circadian system, alters melatonin signaling, and is associated with sleep and mental health disturbances. The pineal gland is central to circadian regulation. However, structural neuroimaging evidence of pineal adaptation to chronic circadian disruption in humans remains limited. This cross-sectional neuroimaging study included 110 healthcare workers, 32 night workers and 78 day workers. High-resolution T1- and T2-weighted magnetic resonance imaging was used to quantify total pineal gland volume, parenchymal volume, and cyst prevalence. Circadian-related sleep disturbance was assessed using the General Sleep Disturbance Scale. Associations with night-work exposure and sleep domains were examined using nonparametric statistical methods. Total and parenchymal pineal volumes did not differ between both workers. However, the pineal cyst prevalence was higher among night workers. Within the night-work group, a greater pineal parenchymal volume correlated positively with sleep-maintenance disturbance. Pineal volume increased during early night-work exposure and subsequently stabilized with longer exposure. Night work was associated with distinct pineal structural features, potentially reflecting morphological adaptations of the human circadian system to chronic disruption. These preliminary findings suggest that pineal morphology could serve as a circadian strain structural marker, but longitudinal studies incorporating direct circadian and hormonal measures are required to establish its biomarker potential.
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Muscle Quality Index (MQI), a novel health metric, is determined by the ratio of handgrip strength to skeletal muscle mass. Despite its potential significance, the association between MQI and circadian syndrome (CircS) has not been explored. This study aims to elucidate the potential association between MQI and CircS. In this study, a cross-sectional analysis was conducted on data from NHANES 2011-2014. And the association between MQI and CircS was explored through a range of statistical methods, including ROC curve analysis, multivariate logistic regression, RCS regression, and subgroup analysis. In this study, a cohort of 2250 American adults was enrolled, among whom 229 individuals (10.2%) were diagnosed with CircS. Both RCS and logistic regression analyses indicated a significant negative linear association between MQI and the prevalence of CircS (OR = 0.35, 95% CI = 0.26, 0.46), as well as its five components, including elevated FPG, elevated BP, elevated WC, reduced HDL, and depression. Subgroup analyses demonstrate that this independent association remained consistent across various demographics and lifestyle factors, including age, physical activity, gender, BMI, and alcohol abuse and smoking status. ROC analysis reveals that, compared to handgrip strength (HGS) and skeletal muscle mass, MQI (AUC = 0.713, 95% CI = 0.678, 0.747) serves as a more reliable factor for identifying CircS. The findings indicate a significant inverse association between MQI and CircS. Promoting physical exercise, especially resistance training, may mitigate the risk of CircS.
Although consumer-grade smartwatches with a photoplethysmograph (PPG) can measure heart rate, their reliability and validity in healthy participants under free-living conditions remain unclear. Therefore, this study compared the heart rates measured by a smartwatch with PPG and a clinically accepted Holter electrocardiograph in healthy adult participants under completely free-living conditions. Ten participants wore a Holter recorder on their left chest and a Garmin vivosmart 5 on their non-dominant wrist simultaneously for 72-96 h. Averages were calculated every 2 min from the data obtained, and timestamps were used for alignment. Agreement between the measurements taken by the two devices was verified using intraclass correlation and Bland-Altman analyses. Error trends for Garmin vivosmart 5 were examined using linear regression analysis. The overall intraclass correlation coefficient range was 0.819-0.937 (mean: 0.902), indicating strong agreement. The mean bias was 1.16 bpm, and the mean limit of agreement was ±12.4 (7.87-20.6) bpm. Furthermore, the linear regression line intercept was negative for all participants, indicating that Garmin vivosmart 5 tended to underestimate the heart rate; however, the slope was positive and close to 0. Overall, the smartwatch maintained a certain accuracy level under fluctuating heart rates and demonstrated reasonable reliability during sleep or daily activities.
Ginger is a potential adjunct therapy for dyslipidemia, but the chronopharmacological evidence is limited. This study systematically evaluated the metabolic and oxidative stress impacts of a highly concentrated ginger extract administered at different circadian phases in mice. By continuous oral administration during the active period (Dark onset, Zeitgeber Time 12, ZT12) and rest period (Light onset, Zeitgeber Time 0, ZT0), we monitored time-dependent effects on body weight, glucose homeostasis, lipid profiles, and reactive oxygen species (ROS) levels in serum and vital organs. We also undertook organ-level analysis to reveal tissue-specific circadian patterns in antioxidant responses. ZT0 ginger administration promoted weight gain, while ZT12 administration significantly reduced random blood glucose and total cholesterol levels. Although ginger universally improved lipoprotein profiles (reducing low-density lipoprotein cholesterol and elevating high-density lipoprotein cholesterol) and suppressed serum ROS regardless of timing, these benefits were consistently enhanced by ZT12 administration. Integrated network pharmacology then identified 107 overlapping targets between ginger's active components and circadian rhythm regulators, with pathway enrichment analysis revealing signaling cascades mainly pertaining to lipid metabolism, followed by oxidative stress and glucose metabolism pathways. These findings substantiate the effect of dose timing on both function and organ specificity, providing a mechanistic basis to study ginger as a useful adjunct therapy for dyslipidemia and, more broadly, for optimizing its use in metabolic health management.
The dromedary is a desert animal that is most active during daylight and rests at night. In its natural habitat, it spends most of the day grazing, whereas in an intensive livestock farming system, food availability is programmed by humans. Temporal feeding exerts a strong influence on the circadian rhythms of numerous species. These aspects have become challenging in camel husbandry, which has recently faced important changes, moving from extensive management with free grazing in the desert to urban and peri-urban intensive farms with various feeding schedules. The objective of the present study was to examine the impact of altering feeding schedules on the locomotor activity (LA), rumination rhythms and the sleep-wake cycle of dromedaries. The study involved four female camels that were housed under semi-natural environmental conditions mimicking an intensive livestock farming system. The study was conducted over three periods of 3 weeks each, with a fixed, non-counterbalanced feeding sequence, during which food was distributed either at 10 a.m. (stages 1 and 3) or at 10 p.m. (stage 2). Behaviour was recorded continuously, and polysomnography (PSG) was performed during the final 48 h of each stage. Shifting food access from 10 a.m. to 10 p.m. induced an increase in the amount of nocturnal activity from 0.6 h (stage 1) and 0.8 h (stage 3) to 4.1 h (stage 2). Conversely, the daytime activity level decreased when food was available during the night. While diurnal rumination remained unchanged, shifting food access reduced the nocturnal duration of rumination from 4.3 h and 4.7 h (stages 1 and 3, respectively) to 2.8 h (Stage 2). Nocturnal feeding was associated with anticipatory bouts of locomotor activity (FAA), which continued for 3 d after switching back to diurnal feeding. Polysomnographic results revealed that nocturnal feeding decreased TST (Total sleep time) during the night, from 27.82% (Stage 1) and 27.04% (Stage 3) to 21.39% (Stage 2). Conversely, a sleep rebound was characterized by a daytime increase in TST from 1.7% and 1.3% to 7.6% when feeding was at 10 p.m. In conclusion, the findings indicate that in camels, nocturnal feeding was associated with marked changes in the temporal organization of LA, rumination, and sleep-wake cycle. While the overall daily amounts of these behaviours were largely maintained, their redistribution across the 24-h cycle suggests that feeding time can modulate circadian outputs. These results highlight the importance of taking into account the natural temporal organization of the species, when designing feeding schedules in camel husbandry, while acknowledging that further studies are needed to assess the long-term physiological and welfare implications.
Attention Deficit/Hyperactivity Disorder (ADHD) remains a neurodevelopmental condition with an incompletely understood etiology, despite evident genetic influences. Disruptions in the circadian cycle and sleep disturbances have been implicated in ADHD. This case-control study aimed to examine the presence of genetic polymorphisms in circadian cycle genes among ADHD patients. Using TaqMan real-time PCR, eight SNPs within circadian cycle genes were analyzed in a sample of 161 Brazilian children and adolescents, comprising 94 ADHD cases and 67 controls. A significant proportion of individuals with ADHD were male (77.6%) and born preterm (18.7%). The most common ADHD subtype was the combined type (60.6%), and Oppositional Defiant Disorder (ODD) was the most frequently observed comorbidity (37.2%). Associations were observed between ADHD and polymorphisms in the PER3 (Period Circadian Clock 3) gene. The C allele of rs228729 (PER3) was associated with an increased risk for the disorder, both in allelic (OR = 2.51 (1.59 - 3.98) and genotypic frequencies (CC homozygote: OR = 8.51 (2.88 - 25.12); TC heterozygote: OR = 4.45 (1.60 - 12.39)). The T allele of rs228727 (PER3) showed an increased predisposition to ADHD OR = 2.69 (1.65 - 4.38); TT homozygote: (OR = 27.50 (3.48 - 216.80)). Haplotype analysis revealed higher frequencies of the C/T (rs228729 and rs228727) in ADHD cases (nominal p = 0.007). No association was detected between the polymorphisms rs934945 (PER2) or rs6927478 (HCRTR2), nor for other PER3 variants (rs707467, rs228644, rs10462020, and rs228697). These findings support an association between PER3 polymorphisms and ADHD; however, given the exploratory nature of this study, further analyses in larger and independent cohorts are required.
This study aimed to examine middle school students' sleep quality based on age, gender, smartphone use, and morningness-eveningness preference. An explanatory sequential mixed methods design was used. The sample included 672 students (368 girls, 304 boys), selected via purposive sampling. Qualitative data were also gathered from 70 of these students. Findings showed that smartphone addiction and morningness-eveningness preference significantly predicted sleep quality. Findings showed that smartphone addiction and morningness-eveningness preference significantly predicted sleep quality. Evening-type (E-type) students, whether addicted to smartphones or not, had lower sleep quality than neither-type (N-type) and morning-type (M-type) students. Among M-type students, smartphone addiction did not significantly affect sleep quality. However, for N-type and E-type students, addiction led to notable differences in sleep quality. M-type individuals used smartphones more before going to bed, while E-type individuals used smartphones more in bed. Statements indicated that smartphone-addicted E-type students (SPA E-types) were more exposed to room and screen light than non-addicted E-types (NSPA E-types). NSPA M-types, in contrast, displayed healthier sleep habits. Students also reported high screen exposure and frequent breakfast skipping, especially outside the NSPA M-type group. Overall, both smartphone addiction and eveningness are associated with poor sleep quality. This situation may negatively affect the development and health of individuals, especially in this age group. SPA E-type students, who are most negatively affected, can be informed about improving their sleep quality by following healthy sleep hygiene practices, such as adhering to regular sleep and wake-up times and reducing smartphone use before bed and in bed.
Seasonal breeders rely on light as a key environmental cue to trigger reproductive activities. While studies have been focused on male white-rumped munia (Lonchura striata), the effects on females are largely unknown. This study examined how light compositions affect female reproductive physiology. In the first experiment, female birds were exposed to short day (SD; 8 L:16D) and long day (LD; 15 L:9D) for a single day to study various transcripts involved in seasonal reproduction. The second experiment included SD and LD along with an added photoperiod of 12 L:12D, and the treatment extended for 30 d. In the third experiment, female birds were exposed to the above three photoperiod conditions, including natural day length (NDL), to assess morphological changes across 18 months. The fourth experiment evaluated seasonal variations in reproductive parameters across four months: March, June, September, and December. The fifth focused on illuminance levels (10, 50, and 100 lux) under a photoperiod of 12 L:12D, and the sixth assessed responses to red (650 nm) and blue light (450 nm) at a constant irradiance of 0.5 W/m2. In all six experiments, an assessment of body mass and follicular diameter was done, while Experiment 3 specifically examined full-body moult and primary flight feather moult as well. Hypothalamic tissue was analysed for reproductive and epigenetic markers. The first experiment revealed enhanced expression of Tshβ and Eya3 in the long-day group, while no significant changes in other reproductive (Dio2, GnRh, Dio3 and GnIh) and epigenetic (Tet1, Hat1, Hdac2, Dnmt1 and Dnmt3b) transcripts were observed. The second experiment observed increased expression of Tshβ exclusively under 15 L:9D, while Tet1, Hat1 and Dnmt1 transcripts were increased under 12 L:12D. Experiment 3 demonstrated distinct morphological responses to different photoperiods, with significant increases in follicular diameter under 15 L:9D and NDL conditions at the 7th month, but this effect was delayed until the 10th month under 12 L:12D. In contrast, no change was observed under 8 L:16D. Seasonal variations in transcripts were noted, with the highest expression of Tshβ, Dio2, GnRh, Eya3, Hat1, Tet1 and Dnmt3b in September compared to other months. The fifth experiment showed that exposure to 100 lux increased key reproductive markers (Tshβ, Dio2, and GnRh) and epigenetic regulators (Hat1 and Tet1), while the sixth experiment found no significant differences between red and blue light treatment. Overall, the findings highlight the importance of light duration and illuminance in reproductive responses. While no robust change in epigenetic transcript was observed under laboratory conditions in female birds, the epigenetic changes observed in the seasonal experiment suggest that seasonal reproductive cycles are under regulation of epigenetic mechanisms at the molecular level.
Delayed-onset muscle soreness can hinder athletic performance by impairing recovery processes. Adequate and restorative sleep plays a crucial role in regulating hormonal balance, cardiovascular adaptation, and muscle tissue repair. However, intense exercise often disturbs sleep quality, thereby prolonging recovery. This study aimed to investigate whether improving sleep quality through melatonin supplementation could indirectly influence recovery parameters, including flexibility, cardiovascular indices, and muscle damage biomarkers, in active athletes. Twenty-four male athletes (18-25 y) from multiple sports, including soccer, basketball, volleyball, and athletics, participated. Participants (N = 24) were randomly assigned to a Melatonin group (3 mg/d for 5 nights before sleep at 10.00 PM, n = 12) or a Placebo group (n = 12). All subjects performed 30 min of eccentric plyometric exercise. Sleep quality was monitored using Fitbit Charge 3 devices, which have been validated against polysomnography for field use. Blood samples were collected pre-exercise and at 24-, 48-, 72-, and 96-h post-exercise to determine CK, IL-6, TNF-α, LDH, MYO, and AST levels. Melatonin supplementation significantly improved total sleep duration, flexibility scores, and resting heart rate compared to placebo (p < 0.05). However, melatonin did not produce statistically significant effects on muscle damage biomarkers (CK, LDH, MYO, AST, IL-6, TNF-α). These findings indicate that melatonin primarily enhances sleep and may aid cardiovascular recovery, with limited direct influence on biochemical markers of muscle damage after acute eccentric overload exercise. Low-dose melatonin supplementation may serve as a supportive, non-pharmacological strategy to improve sleep quality in athletes. While it did not significantly reduce biochemical indicators of muscle damage and cardiovascular recovery, the improved sleep-related recovery suggests potential indirect benefits for overall post-exercise adaptation.
Our study explored the mediating effect of sleep hygiene between morningness-eveningness preferences and psychological distress among a sample of Lebanese adults. A total of 948 Lebanese participants were enrolled in this cross-sectional study (mean age 26.93 ± 10.23 years). A self-administered survey was dispersed using the snowball sampling technique. The survey consisted of socio-demographic characteristics along with the following Arabic validated instruments: The Morningness-Eveningness Questionnaire (MEQ), the Patient-Health Questionnaire (PHQ-4), and the Sleep Hygiene Index (SHI). Statistical analysis was performed using SPSS v.27 with mediation analysis via PROCESS MACRO v.42 Model 4. Sleep hygiene fully mediated the relationship between morningness-eveningness preferences and psychological distress. Greater morningness preferences were significantly associated with better sleep hygiene (i.e. lower sleep hygiene scores). In turn, poor sleep hygiene (i.e. higher sleep hygiene scores) was significantly associated with higher psychological distress. The direct association between morningness and psychological distress was not statistically significant. Our study offered insight on important connections between sleep hygiene, morningness-eveningness preferences, and psychological distress within the Lebanese context. These results highlight the necessity of promoting healthy sleep behaviors and chronobiological awareness to improve mental health in this population.
Bipolar disorder (BD) is a severe mood disorder characterized by seasonal variations, but the underlying metabolite changes are not well understood. This study employed targeted metabolomics to examine serum metabolite changes in 9 BD patients and 9 healthy controls (HCs) at 6 time points: 15 d before, on, and 15 d after the spring equinox and summer solstice. In the summer, 4 metabolites in HCs and 25 in BD showed time effects, with phenylalanine (Phe) -alanine-betaine showing interaction effects; however, none were significant after false discovery rate (FDR) correction. Analysis across the spring and summer revealed significant time effects in 48 metabolites in HCs and 201 in BD, with Phe showing notable interactions. In the spring, Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale scores, retardation, sleep disturbance, and psychic anxiety factors correlated positively with Homoarginine (HArg), Phe, and lactate. In the summer, Young Mania Rating Scale (YMRS) was positively associated with 3-hydroxyphenylacetic acid and negatively with Harg, glutamine, and citrate; sleep disturbance was positively linked to sarcosine, and retardation factor negatively linked to HArg. These seasonal changes in BD metabolites were primarily linked to the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. Further research is needed to understand how these metabolic shifts influence BD episodes.
This narrative review synthesizes evidence on how vitamins, minerals, and amino acids modulate sleep through neurobiological, circadian, and epigenetic pathways. B-group vitamins (B6, B12, folate) are cofactors in the synthesis of serotonin and gamma-aminobutyric acid (GABA). The lack of these factors increases the excitability of neurons and interferes with sleep. Vitamin D exerts its regulation through its nuclear receptor by controlling the key clock genes and melatonin secretion, and suppresses neuroinflammation. Magnesium and calcium modulate neuronal excitability and melatonin synthesis (enhancing GABAergic tone and enzyme activity) to promote slow-wave sleep. Iron and zinc affect the dopaminergic circuits; iron supplementation decreases restless-leg syndrome and sleep fragmentation. Tryptophan and other amino acids stimulate the formation of serotonin/melatonin to reduce sleep latency, and inhibitory amino acids (glycine, GABA) increase central nervous system inhibition to facilitate sleeping. Epigenetic mechanisms that operate on nutrient signals, especially methylation of clock genes using the vitamins folate and B12, are becoming appreciated. Taken together, these mechanisms affect the process of sleep latency, duration, and architecture. The review notes the prospect of more personalized nutritional interventions (possibly personalized by genotyping) in optimizing sleep, but notes that further research is necessary in the form of larger controlled trials.